scholarly journals High Mobility Group Box 1 and Dickkopf-Related Protein 1 as New Biomarkers of Type 2 Diabetes Mellitus: Associations with Increased Glucose Toxicity and Atherogenicity and Lower β Cell Function

2020 ◽  
Author(s):  
Hussein Kadhem Al-Hakeim ◽  
Qasim Jasim Al-Kaabi ◽  
Michael Maes
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Cell Function ◽  
High Mobility ◽  
Related Protein ◽  
Glucose Toxicity ◽  
Wnt Pathways

Background: Type 2 diabetes mellitus (T2DM) is associated with increased atherogenicity and inflammatory responses, which may be related to increased levels of high mobility group box 1 (HMGB1) and Dickkopf-related protein 1 (DKK1). Objective: The role of HMGB1 and DKK1 in T2DM is examined in association with lipid and insulin profiles. Methods: Serum HMGB1 and DKK1 were measured in T2DM with and without hypertension and compared with controls. Results: HMGB1 and DKK1 are significantly higher in T2DM irrespective of hypertension. T2DM was also accompanied by increased atherogenicity indices. HMGB1 and DKK1 are significantly correlated with HbA1c, glucose, indices of insulin resistance, β-cell function, and glucose toxicity, and different atherogenic indices. A large part of the variance in the β-cell index (30.5%) and glucose toxicity (34.8%) was explained by the combined effects of HMGB1 and DKK1 and hypertension. We found that 18.3% of the variance of the atherogenic index of plasma was explained by HMGB1 and DKK1 levels and that 31.2% was explained by glucose toxicity, HMGB1 and body weight. Conclusion: The higher serum HMGB1 and DKK1 levels in T2DM patients and the associations with atherogenicity indicate that low grade inflammation and disorders in the Wnt pathways are associated with T2DM and that both HMGB1 and DKK1 may contribute to increased atherogenicity in T2DM. Moreover, both biomarkers may cause more deficits in β-cell function and increase glucose toxicity leading to the development of more inflammation and diabetic complications. HMGB1 and the Wnt pathways are new drug targets in the treatment of T2DM.

scholarly journals Decreased TCF7L2 protein levels in type 2 diabetes mellitus correlate with downregulation of GIP- and GLP-1 receptors and impaired beta-cell function

2015 ◽  
Vol 24 (10) ◽  
pp. 3004-3004 ◽  
Author(s):  
L. Shu ◽  
A. V. Matveyenko ◽  
J. Kerr-Conte ◽  
J.-H. Cho ◽  
C. H. S. McIntosh ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Cell Function ◽  
Protein Levels

scholarly journals Decreased TCF7L2 protein levels in type 2 diabetes mellitus correlate with downregulation of GIP- and GLP-1 receptors and impaired beta-cell function

2009 ◽  
Vol 18 (13) ◽  
pp. 2388-2399 ◽  
Author(s):  
Luan Shu ◽  
Aleksey V. Matveyenko ◽  
Julie Kerr-Conte ◽  
Jae-Hyoung Cho ◽  
Christopher H.S. McIntosh ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Cell Function ◽  
Protein Levels

scholarly journals SAT-667 Partial Beta-Cell Destruction: An Atypical Case of Immune Checkpoint Inhibitor Diabetes Mellitus

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Zoe Quandt ◽  
Katy K Tsai ◽  
Victoria C Hsiao
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Beta Cell ◽  
Immune Checkpoint ◽  
Beta Cell Function ◽  
Cell Function ◽  
Autoimmune Diabetes ◽  
Insulin Production ◽  
C Peptide

Abstract Background: Autoimmune diabetes mellitus (CPI-DM) caused by immune checkpoint inhibitors (CPIs) is rare- occurring in approximately one percent of patients exposed to this form of cancer immunotherapy. Typically, this immune related adverse event occurs after treatment with PD-1/PD-L1 inhibitors. It is characterized by abrupt insulinopenia leading to acute hyperglycemia. Beta cell autoantibodies are positive in approximately half the cases. DKA is common at the time of diagnosis. Recovery of beta cell function has been reported in only two case reports. In one case, spontaneous resolution occurred following cessation of CPI therapy and in the other the patient was treated with infliximab for concurrent inflammatory arthritis prior to resolution of CPI-DM. Clinical Case: A 50-year-old woman was started on adjuvant pembrolizumab for stage IIIC melanoma following surgery. She had no prior history of diabetes mellitus, thyroid disease, or other autoimmune disease. Pre-infusion random blood glucoses (RBG) were 84 - 105 mg/dL. After 36 weeks, she developed hypothyroidism (TSH 17.5 (0.5-4.1 mIU/L), FT4 6 (10-18 ug/dL)) and started levothyroxine. Pembrolizumab was continued. For nine weeks following her diagnosis with CPI- hypothyroidism, her pre-infusion RBG ranged from 102-133. At 45 weeks (15 cycles) after initiating pembrolizumab, her RBG was 260. She was not on glucocorticoids and had no other signs of inflammation or stress. Pembrolizumab was continued. Just prior to her 17th cycle, 48 weeks after initiating adjuvant pembrolizumab, her RBG was 482 with a normal anion gap and HCO3, and her A1c was 8.9%. Her last dose of pembrolizumab was held. She started metformin and liraglutide. In just three weeks, a random c-peptide was inadequate at 1.7 (0.8-3.5 ng/mL) with a recent RBG of 220 and A1c of 10.3%, showing the acuity and extremity of her hyperglycemia. Over the course of the year, she has achieved excellent glucose control (A1c 6.3-7.1) on this regimen with preservation of insulin production (c-peptides 1.4-1.8 with matched RBG 92-129). She never required insulin. Her beta cell autoantibodies are negative. Clinical Lessons: This is a case of CPI-DM in which the patient did not have complete loss of beta-cell function. The acuity of her hyperglycemia is not consistent with new onset type 2 diabetes. At diagnosis, her c-peptide was inadequate suggesting insufficient insulin production rather than insulin resistance. Therefore, her hyperglycemia is more consistent with CPI-DM than type 2 diabetes. Atypically, she did not progress to fulminant beta cell failure, which could have been due to cessation of pembrolizumab (which is not unique to this case), initiation of liraglutide and metformin, or other unknown immunologic responses that inhibited full beta cell loss. This case raises the possibility of preventing fully insulin dependent CPI-DM if hyperglycemia is caught and treated early.

scholarly journals Diabetic macro- and microvascular disease in type 2 diabetes

2007 ◽  
Vol 4 (2_suppl) ◽  
pp. S7-S11 ◽  
Author(s):  
Michel P Hermans
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Cell Function ◽  
Microvascular Disease ◽  
Patients With Diabetes

Before a patient develops overt type 2 diabetes mellitus, there is typically a prolonged period of patho-physiological change. In the common form of type 2 diabetes mellitus, there are years of insulin resistance, initially compensated by increased beta cell function, then impaired glucose tolerance develops, and finally type 2 diabetes. We know from studies such as the United Kingdom Prospective Diabetes Study (UKPDS) and the Belfast study that loss of beta cell function and insulin resistance are usually relentless.1, 2 Thus, therapy to reduce blood glucose has to be gradually increased with time for patients with diabetes. What is less well known is that every person has a different slope for beta cell function loss which intersects with insulin resistance.

Near-normoglycaemic remission in African-Americans with Type 2 diabetes mellitus is associated with recovery of beta cell function

2001 ◽  
Vol 18 (1) ◽  
pp. 10-16 ◽  
Author(s):  
S. I. McFarlane ◽  
R. L. Chaiken ◽  
S. Hirsch ◽  
P. Harrington ◽  
H. E. Lebovitz ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
African Americans ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Cell Function
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